病理研究

cMicroglia, as the resident immune cells in the central nervous system, exhibit distinct activation states under pathological conditions such as neurological diseases and aging, which are closely associated with neurodegeneration, inflammatory response and other processes. This paper systematically elaborates the classification of microglial activation states identified by RNA-seq technology, and summarizes the core molecular markers of microglia, including CD68, Galectin-3, Cathepsin B, HIF-1α and Axl, as well as their biological functions in phagocytosis, inflammatory regulation and neuronal injury. Meanwhile, a variety of commercial antibodies suitable for experimental detection of the above markers are collated, covering their application scenarios such as Western blot (WB), immunohistochemistry (IHC) and immunofluorescence (IF). This study provides a reference for the selection of specific detection tools and related basic research on microglial activation in neurological disease models.

Macrophages are myeloid cells of the innate immune system that are found in all human tissues in the body and exhibit anatomical and functional diversity. These heterogenous cells are derived from monocyte precursors in the blood that infiltrate into the tissues and differentiate in the presence of cytokines and growth factors.

Cluster of Differentiation 3 (CD3) is a multiunit protein complex expressed on the surface of T cells that directly associates with the T cell receptor (TCR). CD3 is composed of four polypeptides: ζ, γ, ε and δ. Engagement of the TCR complex with antigens presented in Major Histocompatibility Complexes (MHC) induces tyrosine phosphorylation in the immunoreceptor tyrosine-based activation motif (ITAM) of CD3 proteins.

Cluster of Differentiation 3 (CD3) is a multiunit protein complex expressed on the surface of T cells that directly associates with the T cell receptor (TCR). CD3 is composed of four polypeptides: ζ, γ, ε, and δ. Engagement of the TCR complex with antigens presented in major histocompatibility complexes induces tyrosine phosphorylation in the immunoreceptor tyrosine-based activation motif (ITAM) of CD3 proteins. CD3 phosphorylation is required for downstream signaling through ZAP-70 and p85 subunit of PI-3 kinase, leading to T cell activation, proliferation, and effector functions (1).

The immune system has the capability to detect and eliminate tumor cells, most notably through cytotoxic CD8+ T cell recognition of tumor antigens presented on the surface of tumor cells by MHC class I molecules. However, anti-tumor immune cells can be subject to various immunosuppressive mechanisms in the tumor microenvironment (TME).

The interaction between cancer and the host immune system mainly occurs in the reactive tissue stroma surrounding tumors, an area known as the Tumor Immune Microenvironment (TIME). The breakthrough clinical application of immune checkpoint inhibitors, particularly targeted therapies against Programmed Death Protein 1 (PD-1, a T-cell co-inhibitory receptor) and Programmed Death Ligand 1 (PD-L1, also known as B7-H1/CD274), has not only propelled cancer immunotherapy into a new era but also made functional analysis of TIME a core focus in both research and clinical settings. Precise characterization of TIME's cellular composition, functional states, and molecular interaction networks is a crucial prerequisite for screening predictive biomarkers for immunotherapy response. Furthermore, deeply clarifying the dual pro-cancer/anti-cancer mechanisms of various immune cells in TIME and their dynamic associations with tumor cells can provide core support for developing novel immunotherapeutic strategies. However, the high heterogeneity of TIME and the challenge of detecting low-abundance immune molecules pose severe challenges to traditional analytical techniques, urgently requiring highly sensitive, multiplex-targeted in situ detection tools to overcome this dilemma.

The modulation of chromatin structure is an essential component in the regulation of transcriptional activation and repression. Modifications can be made by at least two evolutionarily conserved strategies, through the disruption of histone-DNA contacts by ATP-dependent chromatin remodelers, or by histone tail modifications including methylation and acetylation.

现有研究多聚焦于免疫细胞的浸润丰度与亚型分类，普遍忽略了免疫细胞与肿瘤细胞的空间位置关系，而免疫细胞在肿瘤组织中的空间排布并非随机，而是形成了有序的生态体系，不同肿瘤微环境区域的免疫细胞功能存在显著差异。与此同时，空间转录组、成像质谱流式等高端空间检测技术成本高昂、普及性差，难以大规模应用于临床预后评估与基础研究，因此亟需一种低成本、可量产的技术体系，系统解析结直肠癌肿瘤浸润免疫细胞（TIICs）的原位空间分布规律，明确免疫细胞空间位置对患者预后的调控价值，填补该领域的研究空白。

TSA-mIHC多重荧光免疫组化技术凭借超高灵敏度、多色同步显色、高特异性的优势，成为当下病理科研的核心技术之一。其核心竞争力，源于一套精密且独特的酪酰胺信号放大（TSA）显色反应体系。今天我们就逐层拆解这套显色反应的科学原理，揭开高精度病理染色的底层逻辑。

该研究依托多重荧光免疫组化技术，系统剖析不同GPC3表达水平肝癌的肿瘤免疫微环境特征，旨在明确GPC3的疗效预测价值，为肝癌个体化联合免疫治疗策略优化提供理论支撑。